We are studying the regulation and structure of the genes which code for fibrinogen, the major blood coagulation protein. We have found that fibrinogen mRNA levels are controlled through a complex feedback-like regulation involving the plasmin degradation products of fibrinogen. This regulatory influence somehow coordinates the levels of each of the three fibrinogen mRNAs so that the genes are activated at the same time and to the same extent. We have begun studying the mechanisms underlying this coordinate regulation by study of the structure and nucleic acid sequence of the three mRNAs and the genes which give rise to the three fibrinogen chains. We have also begun studying the human afibrinogenemias and dysfibrinogenemias by cloning and examining the structure of the human fibrinogen genes.